Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by
the letters A, G, C and U.
The others are adenine, cytosine, and guanine.
In RNA, uracil binds to adenine via two hydrogen bonds.
In DNA, the uracil nucleobase is replaced by thymine.
Uracil could be considered a demethylated form of thymine.
Uracil is a common and naturally occurring pyrimidine derivative.
The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting
to synthesize derivatives of uric acid.
Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein;
it was also found in bovine thymus and spleen, herring sperm, and wheat germ.
It is a planar, unsaturated compound that has the ability to absorb light.
Studies reported in 2008, based on 12C/13C isotopic ratios of organic compounds found
in the Murchison meteorite, suggested that uracil, xanthine and related molecules were
formed extraterrestrially.
In 2012, an analysis of data from the Cassini mission orbiting in the Saturn system showed
that Titan's surface composition may include uracil.
Properties In RNA, uracil base-pairs with adenine and
replaces thymine during DNA transcription.
Methylation of uracil produces thymine.
In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability
and improved the efficiency of DNA replication.
Uracil pairs with adenine through hydrogen bonding.
When base pairing with adenine, uracil acts as both a hydrogen bond acceptor and a hydrogen
bond donor.
In RNA, uracil binds with a ribose sugar to form the ribonucleoside uridine.
When a phosphate attaches to uridine, uridine 5'-monophosphate is produced.
Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the
molecule may have from the lack of formal aromaticity is compensated by the cyclic-amidic
stability.
The amide tautomer is referred to as the lactam structure, while the imidic acid tautomer
is referred to as the lactim structure.
These tautomeric forms are predominant at pH 7.
The lactam structure is the most common form of uracil.
Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase
reactions.
Degradation of uracil produces the substrates aspartate, carbon dioxide, and ammonia.
C4H4N2O2 → H3NCH2CH2COO− + NH4+ + CO2 Oxidative degradation of uracil produces urea
and maleic acid in the presence of H2O2 and Fe2+ or in the presence of diatomic oxygen
and Fe2+.
Uracil is a weak acid.
The first site of ionization of uracil is not known.
The negative charge is placed on the oxygen anion and produces a pKa of less than or equal
to 12.
The basic pKa = -3.4, while the acidic pKa = 9.389.
In the gas phase, uracil has 4 sites that are more acidic than water.
Synthesis In a scholarly article published in October
2009, NASA scientists reported having reproduced uracil from pyrimidine by exposing it to ultraviolet
light under space-like conditions.
This suggests that one possible natural original source for uracil in the RNA world could have
been panspermia.
There are many laboratory syntheses of uracil available.
The first reaction is the simplest of the syntheses, by adding water to cytosine to
produce uracil and ammonia.
The most common way to synthesize uracil is by the condensation of maleic acid with urea
in fuming sulfuric acid as seen below also.
Uracil can also be synthesized by a double decomposition of thiouracil in aqueous chloroacetic
acid.
C4H5N3O + H2O → C4H4N2O2 + NH3 COOH(CH)2COOH + NH2CONH2 → C4H4N2O2 + 2
H2O + CO Photodehydrogenation of 5,6-diuracil, which
is synthesized by beta-alanine reacting with urea, produces uracil.
Reactions Uracil readily undergoes regular reactions
including oxidation, nitration, and alkylation.
While in the presence of phenol and sodium hypochlorite, uracil can be visualized in
the blue region of UV light.
Uracil also has the capability to react with elemental halogens because of the presence
of more than one strongly electron donating group.
Uracil readily undergoes addition to ribose sugars and phosphates to partake in synthesis
and further reactions in the body.
Uracil becomes uridine, uridine monophosphate, uridine diphosphate, uridine triphosphate,
and uridine diphosphate glucose.
Each one of these molecules is synthesized in the body and has specific functions.
When uracil reacts with anhydrous hydrazine, a first-order kinetic reaction occurs and
the ring of uracil opens up.
If the pH of the reaction increases to >10.5, the uracil anion forms, making the reaction
go much slower.
The same slowing of the reaction occurs if the pH decreases because of the protonation
of the hydrazine.
The reactivity of uracil is unchanged even if the temperature changes.
Uses Uracil can be used for drug delivery and as
a pharmaceutical.
When elemental fluorine is reacted with uracil, 5-fluorouracil is produced.
5-Fluorouracil is an anticancer drug used to masquerade as uracil during the nucleic
acid replication process.
Because 5-Fluorouracil is similar in shape to, but does not perform the same chemistry
as, uracil, the drug inhibits RNA replication enzymes, thereby eliminating RNA synthesis
and stopping the growth of cancerous cells.
Uracil can also be used in the synthesis of caffeine
Uracil's use in the body is to help carry out the synthesis of many enzymes necessary
for cell function through bonding with riboses and phosphates.
Uracil serves as allosteric regulator and coenzyme for reactions in the human body and
in plants.
UMP controls the activity of carbamoyl phosphate synthetase and aspartate transcarbamoylase
in plants, while UDP and UTP requlate CPSase II activity in animals.
UDP-glucose regulates the conversion of glucose to galactose in the liver and other tissues
in the process of carbohydrate metabolism.
Uracil is also involved in the biosynthesis of polysaccharides and the transportation
of sugars containing aldehydes.
It can also increase the risk for cancer in cases in which the body is extremely deficient
in folate.
The deficiency in folate leads to increased ratio of deoxyuracilmonophosphates/deoxythyminemonophosphates
and uracil misincorporation into DNA and eventually low production of DNA.
Uracil can be used to determine microbial contamination of tomatoes.
The presence of uracil is an indication of lactic acid bacteria contamination in the
fruit.
Uracil derivatives containing a diazine ring are used in pesticides.
Uracil derivatives are more often used as antiphotosynthetic herbicides, destroying
weeds in cotton, sugar beet, turnips, soya, peas, sunflower crops, vineyards, berry plantations,
and orchards.
In yeast, uracil concentrations are inversely proportional to uracil permease.
References
External links Uracil MS Spectrum